title: Desflurane preconditioning induces oscillation of NF-κB in human umbilical vein endothelial cells.
abstract: BACKGROUND
  Nuclear factor kappa B (NF-κB) has been implicated in anesthetic preconditioning (APC) induced protection against anoxia and reoxygenation (A/R) injury. The authors hypothesized that desflurane preconditioning would induce NF-κB oscillation and prevent endothelial cells apoptosis.
  
  
  METHODS
  A human umbilical vein endothelial cells (HUVECs) A/R injury model was used. A 30 minute desflurane treatment was initiated before anoxia. NF-κB inhibitor BAY11-7082 was administered in some experiments before desflurane preconditioning. Cells apoptosis was analyzed by flow cytometry using annexin V-fluorescein isothiocyanate staining and cell viability was evaluated by modified tertrozalium salt (MTT) assay. The cellular superoxide dismutases (SOD) activitiy were tested by water-soluble tetrazolium salt (WST-1) assay. NF-κB p65 subunit nuclear translocation was detected by immunofluorescence staining. Expression of inhibitor of NF-κB-α (IκBα), NF-κB p65 and cellular inhibitor of apoptosis 1 (c-IAP1), B-cell leukemia/lymphoma 2 (Bcl-2), cysteine containing aspartate specific protease 3 (caspases-3) and second mitochondrial-derived activator of caspase (SMAC/DIABLO) were determined by western blot.
  
  
  RESULTS
  Desflurane preconditioning caused phosphorylation and nuclear translocation of NF-κB before anoxia, on the contrary, induced the synthesis of IκBα and inhibition of NF-κB after reoxygenation. Desflurane preconditioning up-regulated the expression of c-IAP1 and Bcl-2, blocked the cleavage of caspase-3 and reduced SMAC release, and decreased the cell death of HUVECs after A/R. The protective effect was abolished by BAY11-7082 administered before desflurane.
  
  
  CONCLUSIONS
  The results demonstrated that desflurane activated NF-κB during the preconditioning period and inhibited excessive activation of NF-κB in reperfusion. And the oscillation of NF-κB induced by desflurane preconditioning finally up-regulated antiapoptotic proteins expression and protected endothelial cells against A/R.
authors.affiliation: Department of Anesthesiology and Critical Care, Zhongshan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yi
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zheng
authors.forename: Changhong
authors.initials: C
authors.lastname: Miao
authors.forename: Jianguo
authors.initials: J
authors.lastname: Tang
authors.forename: Biao
authors.initials: B
authors.lastname: Zhu
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D000077335:Desflurane; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D059748:Proteolysis; D013450:Sulfones / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D018685:Anesthetics, Inhalation; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D000077335:Desflurane; D007530:Isoflurane; D013482:Superoxide Dismutase; D053148:Caspase 3